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EGFR/PPARδ/HSP90 pathway mediates cancer cell metabolism and chemoresistance
Author(s) -
Gou Qian,
Zhang Wenbo,
Xu Ying,
Jin Jianhua,
Liu Qian,
Hou Yongzhong,
Shi Juanjuan
Publication year - 2021
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.29868
Subject(s) - phosphorylation , peroxisome proliferator activated receptor , gefitinib , heat shock protein , cancer cell , cancer research , epidermal growth factor receptor , cell growth , hsp90 , receptor , microbiology and biotechnology , cancer , biology , chemistry , biochemistry , genetics , gene
Epidermal growth factor receptor (EGFR) induces peroxisome‐proliferator‐activated receptor‐δ (PPARδ)‐Y108 phosphorylation, while it is unclear the effect of phosphorylation of PPARδ on cancer cell metabolism. Here we found that EGF treatment increased its protein stability by inhibiting its lysosomal dependent degradation, which was reduced by gefitinib (EGFR inhibitor) treatment. PPARδ‐Y108 phosphorylation in response to EGF recruited HSP90 (heat shock protein 90) to PPARδ resulting in increased PPARδ stability. In addition, PPARδ‐Y108 phosphorylation promoted cancer cell metabolism, proliferation, and chemoresistance. Therefore, this study revealed a novel molecular mechanism of EGFR/HSP90/PPARδ pathway‐mediated cancer cell metabolism, proliferation, and chemoresistance, which provides a strategy for cancer treatment.